In 20-40% of human breast cancers the erbB-2 of neu gene is amplified leading to mRNA and protein overexpression. Amplification of the EGF receptor gene is rare but overexpression of EGF receptor has been shown to occur without accompanied gene amplification. Overexpression of erbB- 2/neu or EGF receptor has been linked to a poorer prognosis for the patient. This poorer prognosis is likely due to a more malignant potential of cells bearing erbB-2/neu or EGF Receptor overexpression. In Phase I, we propose to explore this malignant phenotype by isolating cDNAs corresponding to mRNAs whose level is modulated in cells overexpressing erbB-2/neu or EGR Receptor. We will screen cDNA libraries using probes from the RNA of human tumor cell lines bearing erbB-2/neu or EGF Receptor overexpression. Candidate cDNA will be examined in a three tiered selection system to determine if this corresponding mRNA is consistently altered by overexpression of erbB-2/neu EGFR, or both. In phase II, we will explore the use of these cDNAs as markers of malignancy and to examine their biological role in malignant conversion.